The primary objective of this research is to initiate a systematic investigation into the neurochemical and neuropharmacological alterations that occur in the mammalian brain during the periadolescence period (from shortly before puberty to young adulthood). This is an important developmental period that has been largely overlooked in most developmental neuroscience research. A number of important psychiatric events occur during this period. first, most cases of schizophrenia emerge during adolescence or young adulthood. Second, psychostimulants seem to acquire their euphoriant properties, and possibly their abuse potential, at about the same time. Third, it has not yet been possible, in double-blind controlled studies, to demonstrate the efficacy of antidepressants in the treatment of depression in children and adolescents. Although there may be many clinical and methodological reasons for this difficulty, it is possible that developmental differences in drug response may be at least partially responsible. Understanding the developmental changes that occur in neurotransmitter systems during these periods may provide new insights relevant to our understanding of schizophrenia, stimulant abuse, and depression, and may lead to more effective treatment of adolescents with psychiatric disorders. Our primary focus will be on the periadolescent development of the dopamine system and the prefrontal cortex, as there is evidence that the prefrontal cortex may be functionally impaired in schizophrenia, and that dopamine systems may play a role in both the therapeutic actions and toxicity of antipsychotic drugs. There is also evidence that the addictive properties of stimulant medications is, in part, related to the effect of these agents on dopamine projections to the limbic system and prefrontal cortex. The development of cortical and limbic dopamine systems will be studied using receptor autoradiography, and liquid chromatography. Studies will focus on developmental transitions, gender differences, and the role of testosterone and estrogen in modulating these developmental changes. In the final aim, attention focuses on juvenile depression. An animal model for adolescent depression will be created based on a carefully studied animal model of adult hyposerotonergic depression. The adult model has been shown capable of identifying effective antidepressant drugs with considerable accuracy. We will then ascertain which classes of antidepressant drugs appear to be effective in this adolescent depression model. Overall, these studies should provide fundamental knowledge of key neuropharmacological changes that occur during adolescence, that may be relevant to major psychiatric disorders.